New and developing non-adrenoreceptor small molecule drugs for the treatment of asthma

Abstract

IntroductionInhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas coveredNew and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA.Data was reviewed from studies published up until November 2016. Expert opinionTiotropium improves lung function and has a modest effect in reducing exacerbations when

Cancer-Derived VEGF-C Increases Chemokine Production in Lymphatic Endothelial Cells to Promote CXCR2-Dependent Cancer Invasion and MDSC Recruitment

“…Additionally, disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy in rhabdomyosarcoma, the most common childhood soft tissue sarcoma [29]. In breast cancer, CXCR2 + MDSCs have been shown to promote cancer progression by inducing the epithelial–mesenchymal transition and activated T cell exhaustion [30]. However, how MDSCs are recruited to tumor-draining and distant lymph nodes is largely unknown.…”

Bronchial thermoplasty as a treatment for severe asthma: controversies, progress and uncertainties

“…Currently, the suggestion that bronchial thermoplasty should be considered for patients with severe asthma associated with non-type 2 inflammation and non-eosinophilic inflammation is based on the availability of effective biologics therapies for type 2 inflammation and eosinophilic inflammation, rather than because of evidence that the efficacy of bronchial thermoplasty is related to specific inflammatory phenotypes of severe asthma. Clinical trials that directly compared bronchial thermoplasty, biologics such as omalizumab, anti-IL-5 monoclonal antibodies and novel small molecule drugs [93]…”

The Prostaglandin D2 Receptor CRTH2 Promotes IL-33–Induced ILC2 Accumulation in the Lung

“…Elevated plasma levels of IL-33 have been reported in various human disease conditions, including allergic lung asthma (25,(58)(59)(60), in which ILC2s are known to play a significant role (80,81). In addition, CRTH2 inhibitors can decrease signs and symptoms of allergic lung inflammation in certain patient cohorts but not all individuals (82)(83)(84). Therefore, a better understanding of how the IL-33 and PGD 2 -CRTH2 pathways intersect to promote ILC2 population expansion through proliferation and interorgan trafficking and function of ILC2s in the lung is critical to understanding how CRTH2 inhibitors and other inhibitors that regulate ILC2s could be effectively deployed to alleviate allergic lung inflammation in different human patient populations (82)(83)(84).…”

“…In addition, CRTH2 inhibitors can decrease signs and symptoms of allergic lung inflammation in certain patient cohorts but not all individuals (82)(83)(84). Therefore, a better understanding of how the IL-33 and PGD 2 -CRTH2 pathways intersect to promote ILC2 population expansion through proliferation and interorgan trafficking and function of ILC2s in the lung is critical to understanding how CRTH2 inhibitors and other inhibitors that regulate ILC2s could be effectively deployed to alleviate allergic lung inflammation in different human patient populations (82)(83)(84). Although additional studies using human patient samples will be required to test the role of CRTH2 in various human disease states, our study suggests that CRTH2 inhibitors may be more effective clinically in the context of type 2 inflammation associated with prolonged and systemic IL-33 stimulation.…”